The sympathetic neuron autonomous role of Egr3 in sympathetic target tissue innervation and gene expression

Abstract

Egr3 is a transcription factor that is essential for sympathetic nervous system (SNS) development. Our lab has previously shown that mice with germline loss of Egr3 have profound SNS defects. However, Egr3 is expressed in other cell populations in addition to sympathetic neurons, so it is still unclear whether Egr3 has a critical role specifically in sympathetic neurons. In the present study we show that Egr3 expressed in sympathetic neurons is essential since mice with specific deletion of Egr3 in sympathetic neurons recapitulated the SNS abnormalities seen in the germline Egr3 deficient mice. We also further examined how Egr3 affects sympathetic innervation into target tissues in vivo by utilizing a unique mouse model paradigm. This paradigm enabled us to trace axons from only a small subset of sympathetic neurons allowing the detailed visualization of the innervation pattern of individual axons in target tissues. Since Egr3 is a transcriptional regulator of gene expression we employed microarray analysis to elucidate the downstream genes it modulates in order to control SNS development. We identified several genes involved in both neuron development and cytoskeleton organization. Taken together, these results indicate Egr3 has a sympathetic neuron specific role in SNS development that involves modulating downstream genes affecting how sympathetic neurons innervate target tissues.Support: NINDS, NRSA